Polycyclic aromatic compounds and their metabolites are a well known group of carcinogens which act by linking covalently to DNA. It is not well understood, however, how a particular type of reaction will affect the physical and biological properties of DNA, nor is it appreciated how these events may initiate the carcinogenic process. We will investigate this area, using the aromatic amine N-acetoxy-2-acetylaminofluorene (AAAF) as a representative example. Our objective is to merge the results of conformational potential energy calculations on dideoxynucleoside monophosphate-2-acetylaminofluorene (AAF) adducts and adducts with tetrameric single and double strands, and parallel reactivity studies of AAAF with nucleosides to evaluate which of the many possible AAF-DNA adducts are likely to be responsible for the conformational change that cause the frameshift mutations correlated with carcinogenesis. The effect of pH, concentration, solvent and additives such as free radical generators or quenchers on the type and amount of product produced will be explored. Those adducts which are experimentally observed and are calculated to have significant conformational effects will be synthesized at the dinucleoside monophosphate level, and the predictions tested by NMR and CD studies in solution, and by x-ray crystallographic analysis. Adducts for which these experimental results and theoretical calculations are in accord will be further tested in vivo, using the system of Prof. R.W. Chambers. The dinucleoside monophosphate adduct will be converted by chemical techniques of oligonucleotide synthesis into a fragment of 15 nucleotides. This oligomer will be used as a primer to incorporate the modification into a specific site in the gene G region of infections, double stranded 0X174 DNA. The effect of the modification during replication and repair will be examined in vivo.